Methamphetamine abuse is a major public health problem. Treatment for methamphetamine abuse often succeeds or fails within the first few weeks when the patient just begins to abstain from the drug. Damage to various structures in the brain has been shown in patients abstaining for several weeks to a few years, but little is known about the state of the brain during the critical early weeks. The long-term objective of this proposal is to use neuroimaging to characterize brain structure and metabolism in very early abstinence from methamphetamine in order to improve patient care during recovery. This is highly relevant to the NIH mission to extend healthy life and reduce the burdens of illness and disability. This proposal will use the neuroimaging techniques of Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopic Imaging (MRSI). MRI measures the volumes of structures or "regions" of the brain; MRSI measures the concentrations of several chemicals (metabolites) inside these brain regions. Both MRI and MRSI work non-invasively on living human subjects. This proposal will focus on three brain regions: the parietal cortex, the inferior frontal cortex, and the striatum. Damage or dysfunction has previously been found in each of these three regions in long-term abstinent abusers of methamphetamine. The degree of damage or dysfunction may increase with the amount (grams per week) of methamphetamine habitually consumed by the patient prior to abstinence. In this proposal, MRI and MRSI scans will be performed twice on each of 13 recovering methamphetamine-dependent subjects and 13 age- and gender-matched healthy controls. The specific aims of this proposal are: 1) Determine if volume and metabolite levels of each of the three regions differ between controls and methamphetamine-dependent subjects at 7 days abstinence; 2) Determine if volume and metabolite levels of each of the three regions change in a second scan performed 23 days later (i.e., at 30 days abstinence for methamphetamine-dependent subjects); 3) Within the methamphetamine-dependent subject group, determine if volumes and metabolite levels at scans 1 and/or 2 vary with the grams per week methamphetamine previously consumed. If successful, this proposal will establish whether certain brain abnormalities in methamphetamine abuse are already present in very early abstinence or whether they first appear several weeks into abstinence. If the latter is true, physicians may have to decide whether it is possible and desirable to present these abnormalities from developing with appropriate treatments. Relevance Treatment for methamphetamine abuse often fails within the first few weeks, with the result that methamphetamine-dependent subjects continue to abuse the drug leading eventually to greater public health costs in terms of morbidity, mortality, and patient care expenses. This proposal aims for a better understanding of the state of the brain during very early abstinence from methamphetamine in order to develop novel therapies and improve the success of existing therapies. [unreadable] [unreadable] [unreadable]